SERPINA1
Serpin Family A Member 1 (Alpha-1 Antitrypsin)
Gene Information Card
| Symbol | SERPINA1 |
|---|---|
| Full Name | Serpin Family A Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.13 |
| NCBI Gene ID | 5265 ncbi.nlm.nih.gov/gene/5265 |
| Ensembl ID | ENSG00000197249 |
| UniProt ID | P01009 |
| OMIM ID | 107400 |
| HGNC ID | 8941 |
| Aliases | AAT, PI, PRO2275, alpha1AT, MGC23330 |
Description
SERPINA1 (Serpin Family A Member 1) encodes alpha-1 antitrypsin (AAT), a 52 kDa glycoprotein primarily synthesized in the liver and secreted into the bloodstream. AAT is a serine protease inhibitor that protects tissues from enzymes such as neutrophil elastase. Deficiency due to mutations (e.g., PiZ, PiS) leads to uncontrolled proteolysis in the lungs (emphysema) and accumulation of misfolded AAT in hepatocytes (liver disease).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alpha-1 antitrypsin deficiency | Loss-of-function mutations (e.g., Glu342Lys in PiZ) cause AAT polymerization in hepatocytes, reducing secretion and leading to low serum levels; unopposed neutrophil elastase degrades lung tissue. | ClinVar, OMIM |
| Emphysema (chronic obstructive pulmonary disease) | Deficient AAT fails to inhibit neutrophil elastase, resulting in progressive destruction of alveolar walls. | ClinVar, NCBI |
| Liver cirrhosis | Accumulation of polymerized AAT in the endoplasmic reticulum of hepatocytes causes cellular stress, apoptosis, and fibrosis. | OMIM, NCBI |
| Panniculitis | Neutrophil elastase-mediated inflammation in subcutaneous fat due to low AAT levels. | OMIM |
| Bronchiectasis | Chronic airway inflammation and infection due to protease-antiprotease imbalance. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 100.0 | High |
| Lung | 10.0 | Low |
| Pancreas | 8.0 | Low |
| Kidney | 5.0 | Low |
| Small intestine | 4.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 100.0 | Hepatocellular carcinoma cell line |
| A549 | 12.0 | Lung adenocarcinoma cell line |
| HeLa | 3.0 | Cervical carcinoma cell line |
| K562 | 1.0 | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Glu342Lys (PiZ) | Missense | 1-2% in European populations | Loss of function; causes polymerization and retention in ER, severe deficiency |
| Glu264Val (PiS) | Missense | 2-4% in European populations | Partial loss of function; reduced secretion, mild deficiency |
| Pro369Leu (PiMmalton) | Missense | Rare | Loss of function; intracellular accumulation, severe deficiency |
| Lys256Glu (PiI) | Missense | Rare | Mild deficiency |
| Null variants (e.g., Q0granite falls) | Nonsense/frameshift | Rare | Complete loss of function; no detectable AAT |
Mutation functional classification
Loss of Function (LOF)
PiZ, PiS, PiMmalton, and null variants reduce or eliminate AAT secretion, leading to deficient protease inhibition in the lung.
Gain of Function (GOF)
Not described for SERPINA1.
Dominant Negative (DN)
PiZ mutant AAT can form polymers with wild-type AAT, reducing overall activity in heterozygotes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement and coagulation cascades (KEGG hsa04610)
• Serine protease inhibitor pathway (Reactome R-HSA-1474228)
Protein Summary
Alpha-1 antitrypsin (AAT) is a 418-amino acid glycoprotein with a reactive center loop that inhibits serine proteases, particularly neutrophil elastase. It is synthesized in hepatocytes and secreted into plasma (normal serum levels 1.5-3.5 g/L). The protein has three N-linked glycosylation sites and a characteristic serpin fold. Mutations such as PiZ (Glu342Lys) cause misfolding and polymerization, leading to retention in the endoplasmic reticulum, low serum levels, and tissue damage.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SERPINA1 Knockout HEK293 Cell Line | EDJ-KQ3522 | Human | 5265 | Details Get a Quote |
| SERPINA12 Knockout HEK293 Cell Line | EDJ-KQ10434 | Human | 145264 | Details Get a Quote |
| SERPINA10 Knockout HEK293 Cell Line | EDJ-KQ10951 | Human | 51156 | Details Get a Quote |
| SERPINA11 Knockout HEK293 Cell Line | EDJ-KQ11833 | Human | 256394 | Details Get a Quote |
| SERPINA1 Knockout HCT 116 Cell Line | EDJ-KQ23976 | Human | 5265 | Details Get a Quote |
| SERPINA1 Knockout A-549 Cell Line | EDJ-KQ25354 | Human | 5265 | Details Get a Quote |
| SERPINA1 Knockout HeLa Cell Line | EDJ-KQ54135 | Human | 5265 | Details Get a Quote |
| SERPINA10 Knockout HeLa Cell Line | EDJ-KQ56238 | Human | 51156 | Details Get a Quote |
| SERPINA12 Knockout HeLa Cell Line | EDJ-KQ58518 | Human | 145264 | Details Get a Quote |
| SERPINA11 Knockout HeLa Cell Line | EDJ-KQ59303 | Human | 256394 | Details Get a Quote |
| SERPINA10 Knockout A-549 Cell Line | EDJ-KQ64728 | Human | 51156 | Details Get a Quote |
| SERPINA12 Knockout A-549 Cell Line | EDJ-KQ67007 | Human | 145264 | Details Get a Quote |
| SERPINA11 Knockout A-549 Cell Line | EDJ-KQ67770 | Human | 256394 | Details Get a Quote |
| SERPINA10 Knockout HCT 116 Cell Line | EDJ-KQ73173 | Human | 51156 | Details Get a Quote |
| SERPINA12 Knockout HCT 116 Cell Line | EDJ-KQ75408 | Human | 145264 | Details Get a Quote |
Displaying Records 1 To 15 Of 16 Records
